Tamoxifen induces TGF‐β1 activity and apoptosis of human MCF‐7 breast cancer cells in vitro

Chen, Hongmin; Tritton, Thomas R.; Kenny, Nicholas; Absher, Marlene; Chiu, Jen‐Fu

doi:10.1002/(sici)1097-4644(19960401)61:1<9::aid-jcb2>3.3.co;2-2

Cited by 4 publications

(9 citation statements)

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“…A third possibility is that the cells responding to droloxifene/estradiol are neither in the osteoblastic nor osteoclastic lineages but are secreting a cytokine such as TGF-b that induces apoptosis in pre-osteoclastic cells. A recent report showed that tamoxifen induced TGF-b1 activity and apoptosis in human MCF-7 breast cancer cells in vitro [Chen et al, 1996].…”

Section: Discussionmentioning

confidence: 98%

“…al., 1991]. Droloxifene's antagonism of breast cancer cell growth might also be achieved through apoptosis as has been reported for tamoxifen [Chen et al, 1996]. MCF-7 cells treated with either droloxifene or 17b-estradiol (10 28 M) were assayed for cellular apoptosis using TUNEL.…”

Section: Figmentioning

confidence: 99%

“…Tamoxifen, an estrogen agonist in breast tissue, has been shown to induce apoptosis in human MCF-7 breast cancer cells [Chen et al, 1996]. Apoptosis or programmed cell death serves as a physiological suicide mechanism that preserves tissue homeostasis [Wyllie, 1980;Kerr et al, 1994].…”

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confidence: 99%

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Common mechanism for the estrogen agonist and antagonist activities of droloxifene

Grasser¹,

Pan²,

Thompson³

et al. 1997

J. Cell. Biochem.

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The incidence of postmenopausal osteoporosis is increasing as the population ages. Even though estrogen replacement therapy has proven beneficial in reducing the number of skeletal fractures, the known risks and associated side-effects of estrogen replacement therapy make compliance poor. Recent research has focused on the development of tissue specific estrogen agonist/antagonists such as droloxifene which can prevent estrogen deficiency-induced bone loss without causing uterine hypertrophy. Furthermore, droloxifene acts as a full estrogen antagonist on breast tissue and is being evaluated for treatment of advanced breast cancer. In this report we propose a common mechanism of action for droloxifene that underlies its estrogen agonist and antagonist effects in different tissues. Droloxifene and estrogen, which have identical effects on bone in vivo, both induced p53 expression and apoptosis in cells of in vitro rat bone marrow cultures resulting in a decrease in the number of bone-resorbing osteoclasts. Droloxifene is growth inhibitory in MCF-7 human breast cancer cells and therefore acts as an antagonist, whereas estrogen is mitogenic to these cells and acts as an agonist. Droloxifene, but not estrogen, induced p53 expression and apoptosis in MCF-7 cells. These results indicate that the induction of apoptosis by droloxifene may be the common mechanism for both its estrogen agonist effects in bone and its antagonist effects in breast tissue.

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Section: Discussionmentioning

confidence: 98%

Section: Figmentioning

confidence: 99%

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Common mechanism for the estrogen agonist and antagonist activities of droloxifene

Grasser¹,

Pan²,

Thompson³

et al. 1997

J. Cell. Biochem.

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“…Tamoxifen is a selective ER modulator that is used for the treatment of estrogen-dependent breast cancer. The cytotoxic effect of tamoxifen depends on not only suppression of ER activity but also autocrine induction 23,24 of TGF-β1. Because FOXA1 is highly expressed in ER-positive breast cancer cells, FOXA1 is thought to suppress the cytotoxic effect of tamoxifen by inhibiting TGF-β1-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…The ER antagonist tamoxifen promotes apoptosis of ERpositive breast cancer cells, and this cytotoxic effect depends on autocrine induction of TGF-β1. 23,24 We then examined the effect of FOXA1 knockdown on tamoxifeninduced apoptosis of ER-positive MCF7 cells. FOXA1 knockdown significantly enhanced cell death induced by tamoxifen treatment in MCF7 cells ( Figure 6A).…”

Section: Foxa1 Suppresses the Cytotoxic Effect Of The Breast Cancermentioning

confidence: 99%

Forkhead box protein A1 confers resistance to transforming growth factor‐β‐induced apoptosis in breast cancer cells through inhibition of Smad3 nuclear translocation

Hirata

Takakura

Shibazaki

et al. 2018

J of Cellular Biochemistry

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Transforming growth factor-β (TGF-β) induces apoptosis of normal epithelial cells, such as mammary epithelium. Although breast cancer progression associates with acquisition of resistance to TGF-β-induced apoptosis, the molecular mechanisms underlying this resistance are largely unknown. Here, we show that forkhead box protein A1 (FOXA1), which is known as a pioneer transcription factor, suppresses TGF-β-induced apoptosis of estrogen receptor-positive breast cancer cells. FOXA1 is found to inhibit nuclear translocation of Smad3, a key transcription factor downstream of TGF-β signaling, through suppression of the binding of Smad3 to the nuclear import receptor importin7. Furthermore, RNA sequencing analyses show that knockdown of FOXA1 upregulates Smad3-mediated proapoptotic gene expression. These results demonstrate that FOXA1 as a potent survival factor that suppresses TGF-β-induced apoptosis by inhibiting Smad3 signaling in estrogen receptor-positive breast cancer cells. Thus, we provide evidence for the first time that FOXA1 localizing to the cytoplasm negatively regulates Smad3-induced apoptosis in TGF-β-mediated signal transduction.

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Angiogenesis in breast cancer: The role of transforming growth factor ? and CD105

Guo

Bernabeu

et al. 2001

Microsc. Res. Tech.

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The progression of breast cancer depends on the establishment of a neovasculature, by a process called angiogenesis. Angiogenesis is an invasive cellular event that requires the co‐ordination of numerous molecules including growth factors and their receptors, extracellular proteins, adhesion molecules, and proteolytic enzymes. TGFβ has emerged to be a major modulator of angiogenesis by regulating endothelial cell proliferation, migration, extracellular matrix (ECM) metabolism, and the expression of adhesion molecules. It is a potent growth inhibitor of normal mammary epithelial cells and a number of breast cancer cell lines. It seems that TGFβ exerts pleiotropic effects in the oncogenesis of breast cancers in a contextual manner, i.e., it suppresses tumourigenesis at an early stage by direct inhibition of angiogenesis and tumour cell growth. However, over‐production of TGFβ by an advanced tumour may accelerate disease progression through indirect stimulation of angiogenesis and immune suppression. The cell membrane antigen CD105 (endoglin) binds TGFβ1 and TGFβ3 and is preferentially expressed in angiogenic vascular endothelial cells. The reduction of CD105 levels in HUVEC leads to in vitro angiogenesis inhibition and massive cell mortality in the presence of TGFβ1. CD105 null mice die in utero with impaired vasculature, indicating the pivotal role of CD105 in vascular development. The administration of an immunotoxin‐conjugate, mab to CD105, induces long‐term and complete regression of breast cancer growth in SCID mice. Therefore, CD105 is a promising vascular target for antiangiogenic therapy. Microsc. Res. Tech. 52:437–449, 2001. © 2001 Wiley‐Liss, Inc.

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Tamoxifen induces TGF‐β1 activity and apoptosis of human MCF‐7 breast cancer cells in vitro

Cited by 4 publications

References 0 publications

Common mechanism for the estrogen agonist and antagonist activities of droloxifene

Common mechanism for the estrogen agonist and antagonist activities of droloxifene

Forkhead box protein A1 confers resistance to transforming growth factor‐β‐induced apoptosis in breast cancer cells through inhibition of Smad3 nuclear translocation

Angiogenesis in breast cancer: The role of transforming growth factor ? and CD105

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